Epilepsy‐associated tumours: what epileptologists should know about neuropathology,terminology, and classification systems

Brain tumours are an ever‐challenging issue in neurology and related medical disciplines. This applies in particular to brain tumours associated with childhood‐onset epilepsies, in which seizures are the presenting and only neurological symptom, as our current understanding of the biology and clinical behaviour of an individual tumour is far from being evidence‐based. Prospective and randomized clinical trials are lacking in the field of epilepsy‐associated tumours and a review of the current literature evokes more questions than provides answers. In this review, current areas of controversy in neuropathology, as well as terminology and classification, are discussed from an epileptologist's perspective. An illustrative case report exemplifies this controversy to further promote interdisciplinary discussion and novel research avenues towards comprehensive patient management in the near future.     

Focal cortical dysplasia of Taylor's balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome

BACKGROUND AND PURPOSE: Focal cortical dysplasia of Taylor's balloon-cell type (FCD-BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD-BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery. METHODS: From an epilepsy data bank with 547 histological specimens, 17 FCD-BC were re-evaluated of which high resolution MRI was available. Five additional FCD-BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery. RESULTS: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel-shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD-BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery. CONCLUSION: Focal cortical dysplasias of Taylor's balloon-cell type (FCD-BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable.     

Using orbital sonography to diagnose and monitor treatment of acute swelling of the eyelids in pediatric patients

OBJECTIVE. Clinical signs of acute erythematous swelling of the periorbital region may be related either to benign superficial inflammation or to the more severe and potentially life-threatening condition of orbital infection. CONCLUSION. We recommend orbital sonography in every child with periorbital swelling and erythema. In contrast to superficial infection in which edematous swelling of the eyelid can be documented without lesions of the orbital content, either a hyper- or a hypo-echoic mass displacing the medial rectus muscle laterally is highly suggestive of orbital infection. Introducing sonography into early diagnostic interventions in pediatric patients avoids delaying appropriate treatment and allows disease monitoring on a daily basis.     

The heterogeneity of frontotemporal dementia with regard to initial symptoms, qEEG and neuropathology

OBJECTIVES/METHODS: Ten patients with neuropathologically verified frontotemporal dementia (FTD) were analysed for neuropathological features in relation to first presenting and dominating symptoms, age at onset and duration of dementia, as well as to EEG/quantitative EEG. RESULTS: Cases with a late onset (> 65 years) initially presented language disturbances, while the early onset group (< 65 years) showed predominantly behavioural symptoms and mood alterations as early features. The late onset group presented combined cortical-subcortical degeneration including white matter pathology, while early onset cases showed pathology predominantly in the cortex. EEG was normal in the late onset group, while it was mildly and variably abnormal in those with early onset. CONCLUSIONS: Within this small sample of clinical and neuropathological FTD, cases with late vs early onset differed with respect to initial symptoms, EEG findings and regional distribution of brain pathology.     

Familial presenile dementia with bitemporal atrophy

This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer's disease.     

CD34-immunoreactive balloon cells in cortical malformations

Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylors type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). Whether this intriguing cell type results from similar pathogenetic pathways remains to be shown. Here, we analyzed the immunohistochemical distribution pattern of the CD34 epitope in surgical specimens from 34 patients with FCD IIb, compared to that of 6 patients with TSC and 3 patients with HME. In normal brain, CD34 occurs only transiently during neurulation, but cannot be detected in mature neuroectodermal cell progenies. In contrast, 58% of our patients showed CD34 immunoreactivity within a subpopulation of balloon cells. Interestingly, CD34-positive balloon cells were confined to the white matter, but never observed in neocortical layers. Furthermore, balloon cells expressing neurofilament protein were also restricted to white matter, whereas GFAP-positive balloon cells were observed either in white or gray matter location. Clinical characteristics did not significantly differ between patients with CD34-positive versus CD34-negative lesions. No significant correlation was found between CD34 expression and genetic alterations of the TSC1 gene, which is affected in many FCD and TSC patients and which plays a role in the regulation of cell size. Further studies are warranted to clarify the restricted expression of CD34 in balloon cells of the white matter.     

Cerebral glucose metabolism and early EEG/aEEG in term newborn infants with hypoxic-ischemic encephalopathy

The objective was to investigate how early electrocortical background pattern, as recorded with amplitude integrated EEG (aEEG), correlates with global and regional cerebral glucose metabolism (CMRgl) measured by positron emission tomography during the subacute phase after birth asphyxia. Nineteen term infants with hypoxic-ischemic encephalopathy were investigated. The aEEG background was evaluated at 0-6, 6-12, 12-24, 24-48, and 48-72 h postnatal age, and classified into four categories according to increasing degree of abnormality. The aEEG were also evaluated for sleep-wake cycling and epileptic seizure activity. CMRgl was measured by positron emission tomography with 2-(18F) fluoro-2-deoxy-d-glucose at a median (range) postnatal age 10 (4-24) d. Increasing degree of abnormality in aEEG correlated significantly with decreasing CMRgl: at 6-12 h (-0.593; 0.012) (r value; p value), 12-24 h (-0.669; 0.003), and 24-48 h (-0.569; 0.014) postnatal age. Presence of sleep-wake cycling at 0-6 h (0.697; 0.012), 6-12 h (0.668; 0.003), and 12-24 h (0.612; 0.009) of age correlated with increased CMRgl. Delayed seizure activity at 12-24 h correlated with decreased CMRgl (-0.661; 0.004). Infants with abnormal aEEG at 6-12 h had lower CMRgl in all regions of the brain compared with infants with normal aEEG. CMRgl of any specific region of the brain was not significantly more correlated to aEEG than CMRgl of other regions. Early electrocortical background patterns, early presence of sleep-wake cycling, and delayed seizure activity were highly correlated with global CMRgl measured during the subacute phase after asphyxia, but did not correlate with any specific pattern of regional uptake.